In June of 2023, the combination of Talzenna (talazoparib), a PARP inhibitor, and Xtandi (enzalutamide), an ARPI, was approved for adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC). Based on results from the phase 3 randomized, double-blind, placebo-controlled trial called TALAPRO-2, improvement in radiographic progression free survival of patients treated with the combination of Talzenna and Xtandi compared to treatment with Xtandi alone led to the FDA approval.
Positive topline results from the final overall survival analysis of the TALAPRO-2 study were recently announced indicating a statistically significant overall survival benefit in patients with mCRPC regardless of mutation status. The safety profile of Talzenna plus Xtandi was generally consistent with the known safety profile of each drug.
The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth. Blocking the DNA damage response is most impactful in cancers that already have a deficiency in repairing their DNA. Deficient homologous recombination repair (HRR) is most common when mutations in BRCA1 and/or BRCA2 are present.
All patients should undergo genomic testing to determine whether PARP inhibitors play a role in the management of their cancer. Based on the recent overall survival analysis results, the manufacturer of Talzenna will be seeking review by the FDA to potentially expand the use of this combination in mCRPC regardless of mutation status.
More Reading
PARP Inhibitors – Effective in Men with BRCA-Mutant Prostate Cancer
Connect With Others for Support and Information
Cancer Connect was the first social network created for people with cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed Cancer Connect programs since 1997. Cancer Connect is used by leading cancer centers including Dana Farber to support their patients. Share your experience, ask a question, or start a conversation by joining Cancer Connect.
Reference:
Agarwal N, Azad AA, Carles J. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jul 22;402(10398):291-303. doi: 10.1016/S0140-6736(23)01055-3. Epub 2023 Jun 4. Erratum in: Lancet. 2023 Jul 22;402(10398):290.
https://investors.pfizer.com/Investors/News/news-details/2024/Pfizers-TALZENNA-in-Combination-with-XTANDI-Prolongs-Overall-Survival-in-Phase-3-TALAPRO-2-Trial/default.aspx, Final analysis of TALAPRO-2 to be presented at an upcoming conference.
